I'm Flora Lichtman, and you're listening to Science Friday. Today on the podcast, what does it take to make it to 80, 90, even 100 years old without slowing down? Researchers are studying these older achievers. What can we learn from them? Most people that I know can think of an aunt, uncle, neighbor or friend who is thriving. Oh, you'd never believe they're 80 years old. They're running circles around me.
We're going to talk about super agers. Super agers are those rare seniors who get to old age, but... Somehow they stay young, just like the Golden Girls did. And no cognitive decline for this group, no napping away the golden years. I had one in my family.
Can I cut in? Yes. I would like to hear about your super-ager. Can we honor her? My mother, who lived to 99 plus, and she never considered herself to be old. She used to say, you know, all these old people around me, I don't feel old. And I remember... I remember being with her in the drugstore at the card counter where she was arguing with the clerk because they didn't have a card for her Scrabble player buddy who was 102.
Another super rager. And you have one in your family, right? Yes. My grandmother, Flora Sr., lived to 100, was completely with it all the way, out reading, out doing. out holding court till the very end and an inspiration. If I inherit like 1% of her genes, I would be grateful. I'm with you on this. And because of all of this, scientists are studying these selected seniors to figure out. what's so special about them. Is it the genes? Are they just lucky? Is there some attitude?
And what lessons can we mortals learn? So maybe we can be super-ragers too. And joining us now, my first guest to talk about it is Eric Topol. He's a cardiologist, director, and founder of the Scripps Research Translational Institute. He has a new book. just out called, believe it or not, Super Agers, an evidence-based approach to longevity. Welcome back to Science Friday, Eric. Great to be with you, Ira. Very nice to have you. Let's talk about Super Agers. Why did you write this book?
Well, we've been studying it for a long time. We had done the first whole genome sequence of 1,400 of these folks. They had to be over age 85. They ranged up to age 102. And they couldn't have had any chronic illness or on any medication. So they're hard to find. And what we learned. very different from both of you that have this in your family pattern, is that most of these people did not have it in their genes. In fact, the patient of mine who I present in the book, Lee Rochal, she's 98.
and all her relatives her parents her brothers died in their 50s and 60s that's more likely the pattern so the book is really to put out what do we know about super agers and how are we going to have many more super-agers in the years ahead. Well, what does tie these folks together? Was there a pattern? Well, the pattern is that the lifestyle factors, for the most part... with some exceptions, are very favorable. So we can review those, but of course they transcend diet and exercise and sleep.
The other things, of course, are, and Ira mentioned this, their attitude, their purpose, their sense of... of their own social engagements. They're often frequently out in nature. They're very active people. In fact, what was the thing that was so funny when we were recruiting this cohort is that we had a hard time getting a hold of them because they had so many appointments they were keeping so busy.
So overall, a very sunny disposition, which is really interesting. That's interesting. And they tend to be on the thinner side. So those were the features that we did see in common. And it was very little that we could find in their DNA. There does appear to be something that does explain this, not in their DNA that's biologic, and that's their immune system. Everything points to a very...
resilient, high-integrity immune system that doesn't suffer the usual immunosenescence as we age. Well, would that not be part of your DNA, your immune system? Yeah, because you don't see, yeah, Ira, great point. You don't see that when you just look at the genome sequence. You have to do testing, looking at the B cells, the T cells, antibodies.
So it just doesn't show up in a sequence. It's something you have to actually go after with specific testing. And is it that their immune system, they don't have as much inflammation? What does a good immune system look like? Yeah, that's a great point. So their tendency is not to have untoward inflammation. They also are very good at, for example, fighting cancer cells.
Now we know it's very hard to get cancer, particularly for it to spread, if your immune system is on high alert. And that's one way the immune system kicks in. The other is that... For atherosclerosis, the basis of cardiovascular disease, and for Alzheimer's, it's really that you're having untoward excessive immune response.
in the case of the artery wall for atherosclerosis, or in response to the misfolded proteins like amyloid and tau that can accumulate in the brain. So it's kind of like a Goldilocks. You want to have just the right...
amount of immune response for the right conditions and the super agers seem to have that. That's a particularly great difference of those folks as compared to the elderly right which are the most people most people as we get beyond 60 we have one of these diseases and we're the elderly we want to flip that and get to the welderly
We have another guest to add to the conversation. Emily Rogalski is a clinical and cognitive neuroscientist and the director of the Healthy Aging and Alzheimer's Research Care Center. She's at the University of Chicago. Emily, welcome to Science Friday. Thanks for having me. Emily, how do you define a superager? So superaging is a definition that we defined for research purposes about 15 years ago.
as individuals who are over age 80 but have memory performance at least as good as individuals in their 50s and 60s. So individuals who are older but have youthful memory performance. Is it normal for people to have some memory decline? And sort of how unusual is that, I guess? Yeah. So if we think about really our old thinking of what happened when we age.
dates back to this idea that we thought that individuals just get old and they get senile, and that was the only trajectory of aging. And luckily, we got more sophisticated understanding that neurodegenerative disease or Alzheimer's disease and dementia are an abnormal part of aging. However, along with that came this idea that
there's still this normal trajectory of aging, and with it is associated cognitive decline. It doesn't interfere with our daily living activities. However, there is still this idea that cognitive decline... as we age is inevitable. And while that might be true on average, the idea of super aging really brought to light our true lived experience where
Most people that I know can think of an aunt, uncle, neighbor, or friend who is thriving in their 80s and beyond. And they say, oh, you'd never believe they're 80 years old. They're running circles around me.
And so this idea that individuals can be over age 80 and have really youthful memory performance was something we wanted to quantify. It was really absent in the scientific literature at the time. Well, we have a few of those folks on the line here, maybe somebody's aunt, uncle, neighbor, or friend.
in Ohio. Hi, welcome to Science Friday. Tell us what's on your mind. Well, you asked for people who are super-agers to call you, and so I did. I'm 94. I ran My husband and I started being at Brandywine Falls in the Cuyahoga Valley National Park 37 years ago, and we rehabilitated the house, and I ran it until two years ago.
And some nice people made an offer I couldn't refuse and take over my job at the inn. But I could stay in my room here. So I still live here. Do you have a secret to your super aging? Well, I think running the U probably helped because I had to keep going and solving problems. And we eat very healthily. And we served a healthy breakfast, too. He baked all of our bread.
Wow. So I think it's a combination of that, and I think I'm just probably plain lucky because I'm not on any prescription medications. I feel great. That's great to hear. I also am writing a book, and I've just enrolled at Kent State as a freshman. You're a super-duper ager. Eric, what do you think of that? Thank you, Katie, for calling. Katie is the prototype, Ira. I mean, that's exactly what we found. It wasn't in the genes as much as it is in her, as she described herself.
Just a classic. I mean, that's the patient I present in the book of one of two that I feature. It's just like her, but 98. remarkably crisp, like Emily was saying, in terms of memory. I mean, I knew something was going on because I asked her how she got to the appointment the first time I met her. Of course, she drove. But they're busy. They're doing so many different things. Katie is just right spot on. Katie didn't mention anything about arthritis.
Can you be a super ager and get something chronic like arthritis? Oh, sure. No, I think the main thing is the big three. neurodegenerative cancer and cardiovascular, but no, these people, they're going to have some arthritis, some have glaucoma, you know, things like that, but they just don't have the serious life-threatening diseases. Yeah. Emily, do you look at the brains of super-agers? And if so, do they look different from other aging brains? Absolutely. We actually are able to quantify...
the health of the brain or the youthfulness of the brain from a few different vantage points. When participants enroll into the study, we say they're with us from life and beyond. Because we ask them to enroll and come back over time and then eventually donate their brain at the time of death if they're willing to. And that's really a generous gift, the most generous gift they can give. because we're able to look at cellular and molecular factors that we just can't look at typically during life.
During life, we can measure with MRI scans or PET scans. So we can quantify the thickness of the outer layer of the brain. You can kind of think of that like the bark on the tree. And when we do that in superagers... we see that they are able to retain the thickness that's similar to a 50 to 60-year-old. With one exception, they actually have a region in the anterior cingulate that's thicker in the superagers than it is in the 50 to 60-year-olds.
That region is incredibly important for attention, and attention supports memory, and it gave us one clue of what to look at under the microscope. for when individuals donated their brain. And when we did that, we saw that they have a special type of cells called vonikonomo neurons, these brain cells that are more abundant in the special region of the anterior cingulate.
And those cells are thought to be important for social engagement and social function. And we also see that in general, the cells, their neurons... in the memory regions of the brain tend to be larger, not necessarily more numerous, but larger or plumper. And so these are... the start of measures that we're starting to understand superagers being more healthy from a brain standpoint. Well, from a brain standpoint, when you do these biopsies post-mortem,
Do you ever see super-agers with the symptoms of Alzheimer's, with the tangles that has not affected their lives? Yeah, this is a great question. And for some individuals, we do see some of that pathology. So Alzheimer's pathology is generally...
expected to be there in a lesser amount in individuals who are over age 80. You may see some of those plaques and tangles. We have really a few different pathways that we see in superagers. One is... those that seem to be resistant to the formation of these bad proteins accumulating in their brain so they don't have that Alzheimer's pathology when we would expect a little bit of it to be there.
And then there are other individuals who do have that Alzheimer's pathology in their brain, but it doesn't seem to be having the same effect that we would expect. They're not experiencing that change in cognition. In fact, their memory is really great. Let's go to the phones. George in Brooklyn, New York. Welcome to Science Friday. I'm considering myself at the beginning of being a super-ager. I'm 85, and I feel like I'm in my 60s.
I just came from a trip with 19 other drivers and cars, 2,000 miles in five days, and one of them was a... a place called the Tale of the Dragon, which has 32 miles and 430 turns. And everyone's driving fast, and that was only part of the trip. That took maybe... Half a day. Were you all super-agers here in your trip? No, I was the oldest person there. Everybody would say, God, how can you do this? You're 85.
You're amazing. And I said, well, I've always had a passion for driving. I also do salsa dancing, which is a very intricate thing to do because there are a lot of turns and whatever. Wow. The only thing I have trouble with is, I think, is remembering names, and that's always been an issue with me. I don't think I put enough effort into it, you know? I've had that since 40, so I get it. Thanks, George, for sharing that with us.
this. Eric, these people are just amazing. They really are. And one of the really striking things he mentioned about dancing, but physical activity, when it was compared to... the SSRI antidepressant drugs, which are commonly used. Physical activity outdid drugs by a big margin for relieving depression. And of course, symptoms improving mental health. And as you know, that's a big interaction between physical health. So each time you talk to a person 85 and beyond who fulfills...
this criteria, super aging. You learn about things that are common in this group. It's a fascinating group. And I do think we're going to see a lot more of them in the future because of the tools that we have right now. After the break, why it is important to invest in your social life in your later years. Our brains love to learn new things and our social connections give us that opportunity to engage in complex conversations that keep our brain active. Stay with us.
I'm Lauren Shulgin, host of the 13th Step Podcast from New Hampshire Public Radio. I uncovered sexual misconduct allegations against the founder of one of New England's biggest addiction treatment networks. And then I faced violent retaliation for it. Now, the guy I investigated has been arrested by the feds. I've got all the details on the latest episode of The 13th Step. Listen now wherever you get your podcasts.
Is there a time in a superager's life when you can tell they're going to be a superager? That's a great question, Ira. I think we're going to be able to do that with multimodal AI. with all the person's billions of data points and some that we hopefully will get a chance to discuss. But otherwise, it's pretty hard to do that right now. You're certainly not going to be able to predict it from a family history.
And Emily, do you agree? I would have to agree that I think that's the goal is to try to understand not only who is likely to be a super ager in the future, but how do we help others? be more likely to be on that trajectory. So how do we help individuals live long and live well, not just extending their health, their lifespan, but also matching their health span?
And one of the reasons that we are conducting a multidisciplinary and multi-site study is to help fill in some of those data and gaps around the factors that are key to doing that. Well, this is what I was going to ask. I mean, are there interventions that people should do in midlife, for example, asking for myself to increase your likelihood of becoming a superager, of aging well? Well, Flora, I think, firstly, we do know ways to prevent these three age-related diseases.
80% to 90% from lifestyle and risk factors for cardiovascular, and 40% to 50% for Alzheimer's, neurodegenerative diseases, and also for cancer. So building on that... We have specific ways to prevent these diseases now that not enough people are taking advantage of. So, for example, the story for Alzheimer's disease, if you have a family history... You may have an APOE4 allele, which is a risk factor.
You can have a polygenic risk score for Alzheimer's. And then you can also get a P-tau-217. And there are other of these protein markers. Soon there'll be a brain organ clock. And we can talk more about clocks. There's many layers of data that would establish risk. And Alzheimer's, even mild cognitive impairment, takes 20 years or longer to develop. So we have lots of years of runway. to get ahead of this. And what's also exciting is that these protein markers like P-tow-217
are very responsive to exercise and lifestyle factors. So they not only help to establish risk way in advance, but they give us a way to know whether... The prevention is working. So we're in a whole new time right now to work on building on preventive capabilities for the three big age-related diseases.
So what's the prescription? Exercise? What else? The prescription, you know, for all people, that doesn't work too well. We don't get this adoption of the perfect lifestyle. But when you have a person's risk... stratified and you say, well, you're at high risk, that's when you get adoption of exercise, not just, of course, aerobic, but balance and strength training. That's when you get people attentive to sleep.
health, particularly getting more deep sleep and regularity of their sleep, and also their nutrition in terms of the optimal diet and other factors beyond that. You intervene with lifestyle, your success for people adopting that is when you are working with a specific particularized risk. Let's go to the phones to Melissa in Jupiter, Florida. Hi, Melissa. Hello there. How are you? Fine. Go ahead, please. So I live in Jupiter. My neighbor Eloise is 96 years old. She turned 96 on May 1st.
She is my cocktail buddy. She's my energizer bunny. She is amazing. And I adore her. And I just love having her in my life at 96 years old. Everyone needs a cocktail buddy. Yeah. As a matter of fact, does she have a secret for her longevity and staying healthy? You know, one of the things that she always says, you know what?
I don't care. That's all I got to say is I don't either I don't care. And she also says my only job is to be God's child. And so she lived this beautiful life. She lived alone. She still drives. She needle points. And she's just a lovely, lovely person. And I am so fortunate to have her in my world. You are lucky. Thank you for sharing that with us. And good luck to you and your neighbor.
Let me ask this question of both of you, because as we get older, and I know this in myself as I've gotten older, a lot of the tests, it could be a colonoscopy, it could be something. My doctors tell me I don't get them anymore. I mean, because perhaps it's more dangerous for me to get a test than it is outliving the test. Yet if we're going to be super agers, some of us, and live to 100 and have, let's say,
25, 35 more years, shouldn't I be getting these tests? Emily, what do you think? I do think we need to, you know, understand what is the risk versus the benefit of a procedure and how might it help. But it's also contextualized in this idea of aging stigma and the expectation of how we're going to age. Aging stigma is a real challenge. Superagers really bring this great opportunity to change the expectations and stigma around aging, reminding us that individuals, when they reach a certain age,
there is still more to give. We can learn from them from a wisdom standpoint and they can contribute actively in society. And sometimes we stick a label such as age and then say, oh, we're not doing that because you're over age, whatever. Yeah, that's happened to me. Yeah. I was just going to say, Ira, that it's really not the right idea to just use age as a criterion for either doing tests or abandoning tests as we get older. It really should be defined by the person's risk.
So if you do have a risk for colon cancer that can be established multiple ways, that should be going on throughout one's life. But this whole idea that we should only do mass screening of mammography or colonoscopy by a certain age, this is really... much smarter than that. And we waste so much money. And we also abandon seniors later in their life when we should be still keeping them under surveillance. But do we have enough gerontologists around?
People who know about these issues, not just your family doctor, but people who can take care of you when you get to that over 80 age. We certainly don't. And we also, of course, our medical community isn't well set up for... caring for people in their 80s and beyond, especially making the call like you just had, should I have one of these tests? So, no, we're not well positioned. And we're also not keeping up with how the advances in research are taking us.
Emily, what role does stress play in aging? If someone has a lot of trauma in their life, do they age faster? We certainly know that not only in aging, but really at any standpoint in your life, chronic stress is not good for you. They can result in changes in the... volume of your brain. There are chemical changes that accompany it. And so it's something to pay very close attention to. That said...
The super-agers in our research haven't necessarily lived lives that are free of stress. We have individuals who have encountered tremendous stress in their life, some who have lost children at a young age. others who have been the only survivor of their family from concentration camps. So there's been really tremendous stress that they've encountered, but they've been resilient to it. And so starting to understand...
One's attitude and your resilience to these things is certainly a key area to focus on because we know it's important to brain health, but also general health. I have a little tidbit that I've been wondering about for years because years ago, when we're in our 34th years, I've talked to a lot of gerontologists on this program. And I remember one of them telling me, when you get old...
It's more difficult to get from 70 to 80 than it is from 80 to 90. Is that true? I mean, you find that in your research, Eric? It is true that once you get to 80, your chances of moving on in your years and staying healthy is higher for sure. So it's borne out by the data. Yes. Is socializing, Eric and Emily, is that important, the happiness and the joy and meeting with other people for longevity?
That has been one of the key features that we have seen is really that the superagers endorse this strong social connection with others. This is information that's come to us initially by participants filling out survey data. And we're now in the process of quantifying this. So we ask Super Agers to wear wearable sensors in their daily lives so that we can understand their social connections with others.
and how that is playing such a significant role. And social connection, I think, has other brain benefit too, because when we think about the negative consequences of loneliness and social isolation, which is a huge problem. and aging, the social connection also helps to keep us on our toes. Our brains love to learn new things, and our social connections give us that opportunity.
to engage in complex conversations that keep our brain active. Eric, how should we think about these efforts to reverse aging? Is there anything to that? Well, there's a lot of work being done and a lot of investment by billionaires and others. When they were young, they wanted to be rich. And now that they're rich, they want to be young.
But the problem we have, Flora, is that there's some great science being done in many, many companies that are trying reverse aging. And many of these approaches look very good in mice, even rodents in general. But we have no data in humans. And there's certainly some risks that are involved and certainly lack of proof. I think what's really exciting right now is that the metrics of aging, which is an outgrowth of this science, like this body-wide clock, organ clocks, all these protein markers.
things that Emily has been discussing with respect to what we see in brain imaging, the science of aging has just jumped forward so much. That is what's enabling us to cultivate, nurture. the super agers of the future. Is there enough research? Have the cutbacks in the federal government, Eric? No, that's the problem.
Here we are at this most propitious moment in medical history, and we're seeing these massive cutbacks in resources and grants and people at the agencies at NIH and others. So it's really a total mismatch. Emily? I couldn't agree more. The reason that a lot of this progress has been made is thanks in large part to things like the National Alzheimer's Project Act, which was signed into law.
more than 10 years ago, which changed the landscape of our investment in aging and dementia research. And prior to that, we had so little funding, there couldn't be much diversity in the targets that we were looking at. Thanks to that influx of funding, we now have some FDA-approved treatments. They're not the last line and they're not the panacea for all, but we were making great strides and we stand to, there's a lot of threat right now.
based on the cuts that are proposed. Emily and Eric, are either of you recruiting people, super agers, for your studies? We have a lot listening, obviously. Can they get involved? Should they get involved? We would love for them to get involved. We're recruiting across the U.S. and Canada. They can reach us by either calling or reaching out on our website at HAARC. hark.center.uchicago.edu. Say that one more time. So it's hark.center.uchicago.edu. So H-A-A-R-C.
You need a short link, Emily. I know. Eric, what's in the future for you in this research? Well, I think our efforts are to this use of AI to assemble, integrate all of a person's data, these layers of data that we've been talking about. And what's so extraordinary now... is that it used to be we could say you're at risk, but we couldn't say when in your life. And now everything's changed. We are much better at forecasting whether a person is at high risk, but also when.
Thank you both for taking time to be with us today, Emily Rogowski and Eric Topol. Thank you for your work and for joining us today. Thanks for listening. Don't forget to rate and review us if you like the show. And you can always leave us a comment on this segment on Spotify. We'd love to hear from you. Today's episode was produced by Annette Heist. I'm Flora Lichtman. Thanks for listening.